This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Amyloids are formed when proteins change conformation to form insoluble fibers that cause severe damage and death. Amyloidoses include Alzheimer's and prion diseases including BSE ("mad cow disease"). Mammalian prions are formed by the protein PrP. Amyloids share a cross-beta structure, but have resisted characterization by crystallography and NMR. Fiber diffraction offers the best hope for structure determination;improved methods of specimen preparation and synchrotron radiation offer unprecedented opportunities to obtain improved data. Structural studies are needed to answer fundamental protein folding questions and for drug design. We collected data at BioCARS under the BioCAT/BioCARS agreement in October 2009 and August 2010, and at BioCAT in April 2010. We collected data from the fungal prion HET-s (the first good quality fiber diffraction data from infectious HET-s), from a low-pH form, and from fibrils formed under several extreme conditions. These data show that HET-s and other amyloids are far more polymorphic than had been realized, and that the protein can change form over time. This observation has great significance for understanding of amyloids in general, and for the diseases with which they are associated. We collected data from a 21-residue fragment of PrP, described as a model for infectious PrP. A variety of preparations of the Alzheimer's-associated peptide A[unreadable] all appear to yield the same form, not identical to that reported from ssNMR, although it is related.